Skip to main content
construction release_alert
Images are temporarily unavailable. The scholars team is working with OIT and DHTS to fix the issue.
cancel

Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles.

Publication ,  Journal Article
Liu, H; Tang, X; Srivastava, A; Pécot, T; Daniel, P; Hemmelgarn, B; Reyes, S; Fackler, N; Bajwa, A; Kladney, R; Koivisto, C; Chen, Z; Wang, Q ...
Published in: Nat Cell Biol
August 2015

Robust mechanisms to control cell proliferation have evolved to maintain the integrity of organ architecture. Here, we investigated how two critical proliferative pathways, Myc and E2f, are integrated to control cell cycles in normal and Rb-deficient cells using a murine intestinal model. We show that Myc and E2f1-3 have little impact on normal G1-S transitions. Instead, they synergistically control an S-G2 transcriptional program required for normal cell divisions and maintaining crypt-villus integrity. Surprisingly, Rb deficiency results in the Myc-dependent accumulation of E2f3 protein and chromatin repositioning of both Myc and E2f3, leading to the 'super activation' of a G1-S transcriptional program, ectopic S phase entry and rampant cell proliferation. These findings reveal that Rb-deficient cells hijack and redeploy Myc and E2f3 from an S-G2 program essential for normal cell cycles to a G1-S program that re-engages ectopic cell cycles, exposing an unanticipated addiction of Rb-null cells on Myc.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nat Cell Biol

DOI

EISSN

1476-4679

Publication Date

August 2015

Volume

17

Issue

8

Start / End Page

1036 / 1048

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Time Factors
  • Signal Transduction
  • S Phase Cell Cycle Checkpoints
  • Retinoblastoma Protein
  • Proto-Oncogene Proteins c-myc
  • Promoter Regions, Genetic
  • Phenotype
  • Mice, Knockout
  • Mice, Inbred C57BL
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, H., Tang, X., Srivastava, A., Pécot, T., Daniel, P., Hemmelgarn, B., … Leone, G. (2015). Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles. Nat Cell Biol, 17(8), 1036–1048. https://doi.org/10.1038/ncb3210
Liu, Huayang, Xing Tang, Arunima Srivastava, Thierry Pécot, Piotr Daniel, Benjamin Hemmelgarn, Stephan Reyes, et al. “Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles.Nat Cell Biol 17, no. 8 (August 2015): 1036–48. https://doi.org/10.1038/ncb3210.
Liu H, Tang X, Srivastava A, Pécot T, Daniel P, Hemmelgarn B, et al. Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles. Nat Cell Biol. 2015 Aug;17(8):1036–48.
Liu, Huayang, et al. “Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles.Nat Cell Biol, vol. 17, no. 8, Aug. 2015, pp. 1036–48. Pubmed, doi:10.1038/ncb3210.
Liu H, Tang X, Srivastava A, Pécot T, Daniel P, Hemmelgarn B, Reyes S, Fackler N, Bajwa A, Kladney R, Koivisto C, Chen Z, Wang Q, Huang K, Machiraju R, Sáenz-Robles MT, Cantalupo P, Pipas JM, Leone G. Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles. Nat Cell Biol. 2015 Aug;17(8):1036–1048.

Published In

Nat Cell Biol

DOI

EISSN

1476-4679

Publication Date

August 2015

Volume

17

Issue

8

Start / End Page

1036 / 1048

Location

England

Related Subject Headings

  • Transcription, Genetic
  • Time Factors
  • Signal Transduction
  • S Phase Cell Cycle Checkpoints
  • Retinoblastoma Protein
  • Proto-Oncogene Proteins c-myc
  • Promoter Regions, Genetic
  • Phenotype
  • Mice, Knockout
  • Mice, Inbred C57BL